This application is for funding of a study to characterize the human immune response before and after 2010-2011 influenza A/California/H1N1 seasonal vaccination by developing comprehensive immune profiles utilizing systems biology and bioinformatics approaches. We will develop novel comprehensive immune profiles using a systems biology approach to define specific immune profiles that discriminate baseline, early, mid, and late (homeostatic) innate, humoral, and cellular immune responses after immunization among older adults. Our broad objective is to create comprehensive and innovative immune profiles that explain and predict variations in immune responses to influenza A/H1N1 vaccines. Using novel bioinformatic approaches and a comprehensive assay set (immune outcomes, immune profiles, and immunosenescence markers), we v\/ill create models of immune profiling that are the focus of this application, among pre- and postimmunosenescent subjects. To accomplish these goals, we propose the following specific aims: 1) To describe and characterize longitudinal immune system profiles (Day 0 to Day 75) before and after influenza A/H1N1 vaccination, 2) To identify immune profiles that correlate with vaccine immunogenicity at the humoral and cellular levels Day 0 to Day 75 after vaccination, and 3) To replicate and verify the immune profiles and models discovered in Specific Aims 1-2 in a new replication cohort. This proposal is innovative and significant in that it will: Utilize cutting edge technology that has not previously been applied to understanding influenza A vaccine-induced immune responses. Create comprehensive immune profiles that provide a model and a framework that describe and explain the variability of immune responses to influenza A vaccine in the continuum from baseline, early, mid (peak), and late (homeostatic) immune responses after antigenic challenge. Provide general knowledge important to the development of new influenza vaccines. The end result of this series of aims will be the first systematic immune profiles and models of influenza A vaccine-specific immunogenicity using novel high dimensional technology and bioinformatics approaches, and has the potential to set the standard for analytical methods to understand complex biologic systems. Relevance to Public Health: This grant will provide novel information describing how immune responses to inactivated influenza A/H1N1 vaccine are generated. This information is useful in designing new vaccines to control this deadly viral disease.